Production of sugar c-nitroalcohols



Patented Aug. 30, 1949 PRODUCTION OFVSIUGAR cavirimnconots Johfidliiiton sowae and Hermann out Lauren'z Fischer, Toronto, Ontario Ganada, assignors'to Corn Products Refining company, New York, N. Y., a corporation of New Jersey No Drawing; Application camber 10, 1946', a .ScrialNo. 702,370

1'1 Clainis. (01; 260-433) This invention relates to "the production orc'arg bohydrate C-nitroalcohols, a class'ofc'on'ipounds in which the group ig led,

is incorporated in asuga'r alcohol structure.

An object of the invention is to provide an improved method of producing carbohydrate C- nitroalcohols'. 4 e

first known n1ember of thisclass'of compounds was prepared by the action of alkali and n'itrom'ethane on an acetylated sugar cyanohw drin in methanol solution (Sowden and Fischer, J Am. Chem. SOC.-; 66, 1312 (1944)). The main disadvantage of this method was that the sugar cyanohydrin employed in the reaction had to be synthesized by a series of reactions from a simple carbohydrate. Thus} the cyanohydrin upon which-the successful practice of the-previous method depended-was an expensiveand-diffidul-tly obtainable substar'x'se. Furtl'iermore,--th yield of sugarC nitroalcohol'obtained by such method was rather low.

The present method constitutes an irfiprove ment over' the method previously described. In general, the improved method consistsi'ri efie'ct in'g" chemical reaction, in" the presefice' ofarla kaline reagent, between ah"- aldo's sugar and a; nitropa-raffin. At the conclusion} of the reaction period, the desired productmay be recovered liy several techniques',- hereinafter described.

The reabtion' of the preseht irrvehtion is -b'elieved to" proceed accordiiig to the renew/issuin trative equations:

'D-Arabinose 1-nitro -1-desogy-D'-' sorbit v oxy-Digdannl- Any aldose sugar, as wellas any aldo'se sugar containing substituentswhich may impart thereto increased aldehyde activity, may be usedfo'r pur'posesbf the present invention." Examples of such compounds include D-' and L-arabinose', D'=and'L+xylose', D- ribose, D-glucose, 4,6-benz'ylidene-D-glucopyranose, 2,4' benzylidene L-xyl'opyranose and the'like.

Any nltropa'raflln containing the'group may be used for-purposes of the present-invem tion. Examples of :such compounds include nietroriiethane, nitroethane, nitropropane; and the like.

Alkaline reagents which may be used include sodium metal inm'ethanoLethanol and the like; potassium hydroxide; and equivalents of such reagents, Alkali; salts of substituted-aldose sugars previously specified may also be useditoprovide the necessary carbohydrate reagent for the rei a Q V neatom of sodium or potassium or eq ivalent alkaline material per molecular weight of aldose sugar or derivative thereof is suflicient to bring about a moderately rapid condensation reaction, Whereas two atoms of sodium or potassium-per mole of sugar givea much more rapid reaction Without appreciably afiecfifigthe yield" or prod uct.

Theoretically, one mole of nitroparafl'in is required to react with each mole of sugar in accordance with the present invention. However, nitroparafiins tend to react with alkaline substances to produce undesirable by-products and hence not all of the nitroparafiin is available for reaction with the sugar. Also, the rate of the reaction is increased when more nitroparaffin than that theoretically required is used. .Therefore, in carrying out the present invention, it is 3 desirable and preferable to use a considerable excess of the nitroparafiin over that theoretically required. Any unreacted nitroparaffin may be recovered for reuse in subsequent reactions.

No external heating or cooling of the reaction mixture is necessary. At room temperature, 1. e., about 22 to 28 C., the reaction goes essentially to completion in 24 hours or less when two moles of alkaline agent are used per mole of sugar. At temperatures lower than room temperature, the necessary time of reaction is longer although no appreciable difference in yield is apparent. Elevated temperatures are not desirable due to the resulting rapid disappearance of the nitroparaffins under the influence of alkali and the production of undesirable colored by-poducts. In general the temperature at which the reaction is effected should not exceed about 40 C.

Commercial or reagent grades of the reactants, the alkaline agents and the mutual solvents or reaction media heretofore mentioned are satisfactory for purposes of the present invention.

However, they should all be in substantially anhycrystalline and in other instances, they are liquids or sirups.

The product obtained from the condensation reaction when a benzylidene derivative is used as one of the reactants is a benzylidene carbohydrate C-nitroalcohol. This may be converted to the unsubstituted sugar C-nitroalcohol by hydrolyzing off the benzylidene group with a dilute mineral acid, such as dilute sulfuric acid. This procedure has been described in J. Am. Chem. Soc 66, 1312 (1944) and is not claimed as part of this invention.

Sugar C-nitroalcohols produced in'accordance with the present invention will contain one more carbon atom than the sugars from which they are derived when the nitroparaflin used is nitromethane. The nitro group may be eliminated from the sugar C-nitroalcchol in each case by adding an alkali salt solution thereof to a moderately concentrated sulfuric acid solution to produce an aldehyde group. (J. Am. Chem. Soc.,

66, 1312 (1944)). The present invention, there fore, constitutes a means of lengthening a sugar chain. The properties of several sugar C-nitroalcohols are also described by Sowden and Fischer in the aforementioned publication and also in J. Am. Chem. 800., 67, 1713 (1945) and ibid. 68, 1511 (1946).

Theoretically, two isomeric sugar C-nitroal= cohols arise from any one aldose sugar used in the reaction with nitromethane. However, all the isomers possible of formation have not been isolated. Thus, where 4,6-ben5zylidene-D-g1ucopyranose was used as a reactant with nitromethane, 5,7 benzylidene-l-nitro-ldesoxy-D- alpha-glucoheptitol was isolated, but not the corresponding D-beta-glucoheptitol derivative.

When nitromethane and 4,6-benzylidene-D- glucopyranose were used as reactants, another typ of nitroalcohol than heretofore described, 6. g., 5,7-benzylidene-2,6-anhydro-1-nitro-1-desoxyglucoheptitol, was isolated. (See Example This compound is not one of the isomers to be expected normally from the reaction. From this compound 2,6-anhydro-1-nitro-1-desoxyheptitol was prepared. (See Example 16.) The structure of 2,6-anhydro-1-nitro-1-desoxyheptitol is as follows:

CHQNOZ 1 ts sir l which is intended to be limited only in accordance with the scope of the appended claims.

PREPARATION or l-NITRO-l-DESOXY-D-MANNITOL AND 1-NI'rRo-1-DEs0xY-D-SoRBIroL Example 1 To a suspension f 50 grams of D-arabinose in ml. of methanol and 180 ml. of nitromethane was added 10.5 g. of sodium in theform of sodium methoxide in 350 ml. of methanol. The sugar dissolved rapidly and an amorphous precipitate began to form a few minutes later. After the mixture was shaken for 18 hours at room temperature, the precipitate was separated therefrom by filtration and was washed with a mixture of equal parts of methanol and ethyl ether, then with ethyl ether and finally with petroleum ether. There was obtained 83 g. of dry material containing 9.1% of sodium by analysis. a

This product was dissolved in 400 ml. of water and then was passed through a column of an ion exchange resin (sold under the trade name of AMBERLITE-I.R.-100-A. G. by Resinous Products Corporation) sufiicient to remove the sodium ions. The resulting solution was concentrated at reduced pressure and allowed to crystallize.

Fractional recrystallization of the crystals thus obtained from absolute ethanol yielded the following crystalline fractions:

A 28.2g M. P. 124-129 C.

B 8.3 g. M. P. -107 C. v

C 12.1 g M. P. 95-135 C. (crude mixed nitroalcohols) Fraction A, upon recrystallization from absolute ethanol, yielded pure l-nitro-l-desoxy-D-mannifllii'mlt. of solution) was +7.0'. The yield was 18.5%. l-Nitro-l-desoxy-Ls-sorbitoL, P. 108 to 109 C, (5 in water (concentration 6.7 g. per 100 *ml. of solution-9' was +9.5. The yield was 3.81 70. 1 Pan?amnion. or '1-N1TR0.-l-DEsoxY-D-GULIToL AND. I-NI'rRo-l-DEsoXY-D-IDI'roL.

Examples" *Whfen -1 -"g-. of 'lD-"x'ylosewas' treated in a. manner similar to-that described above in Example 1, there was-obtained 1655s. of a mixtureof the amorphous sodiumsalts of l-nitro-I-desoxy-D- glul-it'ol and"1-nitro--1=-desoiry-D iditol, containing 9 .1% ofsodium. Removal ofthe sodium ionby means di a suitable ion 'exchange resin then gave: thecriide'miked nitroalcohols a-sa colorless sirup.

PREPARATION or 6- Nr rao6 DssoxY-LrSoaBrroL.

AND 6-NI'JIRQfi-DESQXY-L-IVIIXNNITOL Examplerel- When 7--g;of'L-xylose was'tr'eated similarly to the above examples; there was obtained 6.75- g. ofi'a mixture: of. the sodium: salts of 6-nitro-6- desoxy-L-sorbitol and: 6-nitro-6-desoxy-L-mannitol, containing 911% o sodium, Removal of the sodium ion by means of a suitable ion exchange resin then gave thecrudemixed nitroal'cohols as'a' colorlesssirup. r v

PREPARATION or:l-Nmzm1.-D.EsoXY D-ALLIror;

ExampZeFS 7 When l flgn-of fl-ribose wa'sft re'ated similarlyto the asoveexammes, there-wasobtained 14 g. of amixture 'of-thesodium saltsof -l nitro-r-desoxy D allitol' and l nitro Idesoicy-D-altritol; conta1ning-9:3% ofsodium; Thesewereconverted as in'the-above-examples to the colorless, 'sirupy crude] nitroalcohols. Y

or Zet-Bnnznmnim;GeNfiao-G LBREPARATION Dnsox-Y-D- SOR-B-ITOL -24;benzylldene-hsxylopyranose1 was: prepared: from 2,4-benzylidene-D+sorbitol, acoording to the" method described by v.. Vargha (Ber. 68, 18, 1377 (1935)). 53.7 g. of'this'ma'terial in sirupy form was dissolved; in a suitable glass:container; in a mixture'of l liter of absolute methanol' and 160" m1: 0f nitroniethane (reagent grade). To this was aidded g; of sodium as sodium' m'ethoxide in 800" ml -;ofabsolute methanol} The entire-mikturewas-allowed to sta-n'dfor 22 hours at room temperature after- 'which 27 ml; of glacial acetic acid was added thereto. The resultant was thenv concentrated at reduced pressure. Some crystals formed during. this operation and upon allowing the concentrated liquor to cool,

. more crystals formed. Thesecrystals were purifled by recrystallizationonce from: water, a total of 34 g- (50% being obtained. They were'identi fled as ZA-benzylidene-Gsnitro fi-desoxy-bssorbitol. The melting'pointthereof. was 192 to 194' and (@51 water (concentration 1 g. per 106 mLJot solution) was 4-.4.

' Example 7" When crystalline 2.4-benzylidene-L-xylopyranose (M. 1?. about 180 G.)- was substituted for thesirupy material usedin Example 1 a yieldof 51% of the crude 2,4-benzylidene-fi nitro-fidesoxy D-sorbitol was obtained.

Fimsnseeion or 6-mTRo=6-DEseXY-D-Sbmrrma V Fnoiu ZA-Bmmrnms s mcao finssoxwn- Soasrronl Example 8- To .1(I g. or; 2,4-benzylidene-G-nitro-G-desoxy- D-sorbitol prepared according; to Example 6 was added. 100 ml. of (3.1. N sulturic acidand the mixture was. heated at 7-5 to C. for Lhour. j Themixture was then: cooled and the liberated benzal dehyde was removedby extraction with ether. Barium carbonate was added to neutralize the sulfuric acid and the barium sulfatewhich-mecipitated was removed by filtration.- The clear solution remaining. evaporated. at reduced pressure, toclryness. The sirupremaining.-crys tall-ize spontaneously after several days.

The crystals wererecrysiaallizedirom EJIliX-tllfle consisting of ethyl acetate and a small amount of methanol. There was: obtained 5.56 g. (79%) of 6-nitro-6-desoxy-D-sorbitol which showed a melting' point. of 78 to 8010. When: the 6-11'itro-6- desoxy-D-so-rbitol was crystallized several times either'from dryethylacetate or firm! dry 'butanol, two types of crystals'were' obtained from such successi've re'crystallization from each solvent. The onetype'was in the form of fine. needles melting at Blto 83C. and the other; type was in 'the'form of hard, compact prisms-meltingat '89 to 91 C; The two forms were interchangeable by appropriate conditions of concentration, rate of cooling or inoculation of theii solutiori'sand bath-showed ("001 5 in water- (concentration 5-=-gr. per m1; of solution) -7 .9.' They were, therefore, dimorphic crystalline forms of the samesubstance. The proof of the structure and properties=of 6-nitro fi desoxy-D sorbitol have'beendescribed'by Sowden and FischerKJ. Am. Chem. Soc, 67,1713 (1945)).

Base/ emma on 5;-7-Bc1 rzYmDENE-1.-Nmio- 1 DESOXY-D-ALPHA-GLUCOHEPTITOL Example -9- 100 g. of 4,6-benzylidene-D-glucopyranose was dissolved, in a suitable glass container, in a mixture consisting of 1500" ml ofabsolute methanol and 250 ml. of nitromethane (reagent grade) and to the resultingeso'lution was 'added 1 liter of absolute methanol containing 17.3 g. of sodium as sodium methoxide. After standing for 8 hours at room temperature, the-solution was acidified with 47 ml. of glacial acetic acid and was then concentratedat -reduced pressure toazsir-up To the sirup was added 200 ml oiiwaterc- Theiresult ingsolution'wasconcentratedat reducedpressure until all of the methanol and' unreactedinitro meth-anei'had' been removed:- The resulting-con centrated aqueous solution was cooled; whereupon a crystalline product formed. The crystalline product was separated by filtration and washed with ice water. There was obtained 25.9 g. (21%) of crude crystals which were identified as 5,7- benzylidene-l-nitro-l-desoxy-D-alpha-glucoheptitol. After this product was crystallized once from water and several times from a mixture consisting of equal partsof ethyl acetate and petroleum.ether,. it showed a melting pointof 160 to 162 C. from water (concentration 1.1 g. per 100 m1. of solution) was -42.5.

Example The crystalline sodium salt of 4,6-benzylidene- D-glucopyranose was prepared by the method of Zervas, Ben, 64, 2289 (1931); 114 g. of this salt, containing 1 mole of sodium per mole of sugar, was dissolved, in a suitable container, in a mixture of 315 ml. of nitromethane (reagent grade) and 2000 ml. of commercial synthetic methanol. The solution was allowed to stand at 10 to 12 C. for 187 hours. Thereafter, 25 m1. of glacial acetic acid'was added to the solution and the entire resulting mixture then concentrated at reduced pressure to a'si'rup. The resulting sirup was dissolved in about 500 ml. of Water and concentrated at reduced pressure to about 200 ml. The concentrated sirup was cooled, whereupon crystalline 5,7-benzylidene-1-nitro-l-desoxy-D-alpha-glucoheptitol formed. 37.7 g. (29%) of the crude product was obtained. The crude product was purified by recrystallizing once from water. The purified product showed a melting point of 161 to 163 C. 100 ml. of solution) was 42.5.

Example 11 Example 12 To 8.1 g. of 4.6-benzylidene-D-glucopyranose dissolved in about 100 ml. of methanol containing 25 ml. of nitromethane was added 1.4 g. of sodium, as sodium methoxide, in about 100 ml. of methanol and the entire mixture then made up to 250 ml.

by the addition of methanol. As the reaction proceeded at room temperature, the specific opti cal rotation of this mixture, based on the benzylidene glucose, showed the following successive values Specific Elapsed Optical Time Rotation Ali-mites Degrees After 5 hours, the mixture was acidified with 4 ml. of glacial acetic acid. Upon concentration in the manner described in the previous examples there was obtained 2.04 g. of crude 5,7-benzylidene-l-nitro-l-desoxy-D-alphaeglucoheptitol.

(00 in water (concentration 2 g. per

. Erample 13 f To 8.0 g. of 4,6-benzylidene-D-glucopyranose dissolved in about 100 ml. of commercial absolute ethanol containing 25ml. of nitromethane was added 2.4 g. of potassium hydroxide dissolved in about 100 m1. of absolute ethanol, and the solution was then made up to 250 ml. by the addition of absolute ethanol. After the solution was allowed to stand for 5 hours at room temperature, it was acidified with 4 m1. of glacial acetic acid. Upon concentration in the manner described in the previous examples, there was obtained 1.3 g. of crude 5,7-benzylidene-l-nitro-l-desoxy-D alpha-glucoheptitol. After recrystallization from water the product showed a melting point of 160 to 162C. and (11) in water was 41.

PREPARATION or 1-N1rRo-1-DEsoxY-D-ALPHA-Gr.'oooHEPrIroL FROM 5,7BENZYLIDENE1-NITRO-1- DESOXY-D-ALPHA-GLUCOHEPTITOL Example 14 A mixture of 5 g. of 5,7-benzylidene-l-nitro-ldesoxy-D-alpha-glucoheptitol, and ml. of 0.1 N sulfuric acid was heated at 70 to 75 C. for 40 minutes and then at 100 C. for 15 minutes. After cooling, the mixture was extracted with ether to remove the liberated benzaldehyde. Barium carbonate was added to neutralize the sulfuric acid and the barium sulfate which precipitated was removed by filtration. The clear solution remaining was concentrated to dryness at reduced pressure. The residue thereby obtained was recrystallized from ethanol and there was obtained 2.8 g. (77%) of 1-nitro-1-desoxy-D-alpha-glucoheptitol which showed a melting point of- 138 to 139 C. (00 in water (concentration 6.4 g. per 100 ml. of solution) was +3.1.

The proof of the structure and the properties of l-nitro-1-desoxy D-alpha-glucoheptito1 have been described by Sowden and Fischer (J. Am.

Chem. 300., 68, 1511 (1946) PREPARATION or 5,7-BENzYLInENE-2,6-ANHYnRo-1- Nrrno-l-Dnsoxxrrrzrrrror.

Example 15 A mixture containing 126 g. of 4,6-benzylidene- D-glucopyranose, 250 m1. of nitromethane, 3160 ml. of methanol and 21.7 g. of sodium, as sodium methoxide, was allowed to stand for 24 hours at room temperature. Thereafter, the mixture was acidified with a slight excess of glacial acetic acid. Then the mixture was concentrated at reduced pressureuntil a sirupy residue was obtained; A small amount of crystalline material formed in the sirupy residue. Water was added thereto and the crystals removed by filtration. The crude crystals were dissolved in methanol and then precipitated from the methanol by the addition of water. The crystals obtained weighed 7.22 g. (5%) and were identified as 5,7-benzylidene 2,6 anhydro 1 nitro 1 desoxy heptitol. After another recrystallization from aqueous methanol, the crystals melted at 211 to 212 C. and (00 in methanol (concentration 1.3 g. per ml. of solution) was '35.4.

Example 16 The procedure of Example 15 was followed except that the mixture was allowed to stand 18 days at 6 to 8 C. before it was acidified. 'Ihere was obtained 3% of 5,7-benzylidene-2,6-anhydrol-nitro-l-desoxyheptitol. After separation of the aforementioned compound, the remaining liquor was treated in accordance'with Examples-9, 10,

9 11. 12 and 13 and there was obtained 19% of 5.7- benzylidene 1 nitro 1 desoxy D alphaglucoheptitol.

PREPARATION or 2,6-ANHYDRO-l-NITRO-l-DESOXY- nsrrrror.

Example 17 A'solution of 1.2 g. of ,7-benzylidene-2,6- anhydro-Lnitro-l-desoxyheptitol in ml. of 0.1 N sulfuric acid was heated at 100 C. for one hour. Thereafter, the mixture was treated to remove the liberated benzaldehyde and the sulfuric acid as described in Examples 8 and 14. There was obtained 0.66 g. (77%) of 2,6-anhydro-l-nitro-1-desoxyheptitol' which showed a melting point of 177 to 177.5 C. and M in water (concentration 3.7 g. per 100 ml. of solution) was +8.2.

The proof of the structure of 2,6-anhydro-1- nitro-1-desoxy heptitol has been described by Sowden and Fischer in J. Am. Chem. Soc., 68, 1511 (1946).

PREPARATION or 1-NI'1RO-l-DESOXY-D-ALPHA- AND BETA-GLUCOHEPTITOLS Example 18 To 10 g. of powdered D-glucose suspended in a mixture of 100 ml. of methanol and 50 ml. of nitromethane was added 2 g. of sodium, as sodium methoxide, in 100 ml. of methanol. The mixture was shaken for 22 hours at room temperature and was then acidified by the addition thereto of 6 ml. of glacial acetic acid. Thereafter the solution was concentrated at reduced pressure, about 200 m1. of water was added, and the concentration at reduced pressure was continued until the volume of the solution was reduced to 100 ml. The solution was then passed through a column of an ion exchange resin (sold under the trade name of AMBERLI'IE-I. R.-100- H-A. G.) suflicient to remove the sodium ions present. The solution was then treated with a decolorizing carbon and was then concentrated at reduced pressure to a nearly colorless sirup. This sirup contained a mixture of l-nitro-l-desoxy- D-alpha-glucoheptitol and l-nitro-l-desoxy-D- beta-glucoheptitol and some unchanged D- glucose.

PREPARATION or 1METHYL-1NITRO-1-DESOXY-L- SORBITOL AND 1METHYL-l-NITRO-l-DESOXY-L- MANNITOL Example 19 To a suspension of 5 g. of L-arabinose in a mixture of ml. of methanol and 25 ml. of nitroethane was added 40 ml. of methanol containing 1.1 g. of sodium. The mixture was shaken at room temperature for 25 hours and a clear solution resulted. To this solution was added 200 ml. of ethyl ether (U. S. P, grade). The resultin amorphous precipitate was filtered and washed in succession with a, mixture of equal volumes of methanol and ethyl ether, then with ethyl ether and finally with petroleum ether. The precipitate was dried in vacuo over phosphorus pentoxide. There was finally obtained 7.0 g. of a white hygroscopic powder consisting of the mixed sodium salts of the desired sugar C-nitroalcohols, e. g., l-methyl-l-nitro-l-desoxy-L-sorbitol and l-methyl-l-nitro-l-desoxy- L-mannitol. The amorphous salts contained 9.1% of sodium by analysis, (theory 9.3%).

When treated. with nitrous acid the powder consisting of the above-mentioned sodium salts 3. The process which comprises effecting chemical reaction between an aldose sugar and nitromethane by contacting in intimate admixture said sugar and said nitromethane in the presence of an alkaline agent under substantially anhydrous conditions at a temperature not exceeding about 40 C.

4. The process which comprises efi'ecting chemical reaction between aldopentose and a nitroparafiin containing the group by contacting in intimate admixture said aldopentose and said nitroparafiin in the presence of an alkaline agent under substantially anhydrous conditions at a temperature not exceeding about 40 C.

5. The process which comprises effecting chemical reaction between an aldohexose and a nitroparafiln containing the group by contacting in intimate admixture said aldohexose and said nitroparaffin in the presence of an alkaline agent under substantially anhydrous conditions at a temperature not exceeding about 40 C.

6. The process which comprises effecting chemical reaction between a benzylidene substituted aldose sugar and a nitroparafiin containing the group I CHNO2 by contacting in intimate admixture said aldose sugar and said nitroparaffin in the presence of an alkaline agent under substantially anhydrous conditions at a temperature not exceeding about 40 C.

7. The process which comprises eifecting chemical reaction between 4,6-benzylidene-D- glucopyranose and. a nitroparaffin containing the group I -CHNOa by contacting in intimate admixture said 4,6- benzylidene-D-glucopyranose and said nitroparafiin in the presence of an alkaline agent under substantially anhydrous conditions at a temperature not exceeding 40 C.

8. The process which comprises effecting chemical reaction between 4,6-benzylidene-D' glucopyranose and nitromethane by contacting in intimate admixture said 4,6-benzy1idene-D- glucopyranose and said nitromethane in the presence of potassium hydroxide under substantially anhydrous conditions at a temperature of about 22 C. to about 28 C.

9.'The process. which comprises eflfecting chemical reaction between xyiose and nitromethane by contacting in intimate admixture said xylose and said nitromethane in the presence of sodium methoxide under substantially anyhdrous conditions at a temperature of about 22 C. to about 28 C. and recovering the product resulting from said reaction.

10. The process which comprises effecting chemical reaction between glucose and nitromethane by contacting in intimate admixture said glucose and said nitromethane in the presence of sodium methoxide under substantially anhydrous. conditions at a temperature of about 22 C. to about 28 C. and recovering the product resulting from said reaction.

11. The process which comprises efifecting chemical reaction between 4,6-benzylidene-D- glucopyranose and nitromethane by contactin presence of sodium methoxideunder substantially anhydrous conditions at a temperature of about 22 C. to about 28 0., and thereafter treating the resultant 5,7-benzylidene 2,6-anhydro-1- nitro-l-desoxyheptitol with sulfuric acid at a temperature of about 100 C.

JOHN CLINTON SOWDEN.

HERMANN OTTO LAURENZ FISCHER.

REFERENCES CITED The following references are of record in the file of this patent:

Sowden et al., Journal American Chemical Society, vol. 66, August 1944,'pages 1312 to 1314.

Number 

